title: High levels of TNF, soluble TNF receptors, soluble ICAM-1, and IFN-gamma, but low levels of IL-5, are associated with hepatosplenic disease in human schistosomiasis mansoni.
abstract: In a case-control study based in two areas of Kenya, hepatosplenic schistosomiasis mansoni was shown to be linked with low levels of IL-5 and with correspondingly high IFN-gamma, TNF, and circulating soluble TNF receptor I (sTNFR-I), sTNFR-II, and sICAM-1. PBMC from the hepatosplenic cases responded to in vitro Ag stimulation with significantly higher levels of IFN-gamma and TNF, but lower levels of IL-5, compared with nonhepatosplenic controls matched for age and infection intensity. Most of these correlations were confounded by differences between geographical areas. However, principle component analysis identified a high IFN-gamma and TNF, and low IL-5 axis in the data as the first principle component; this was significantly associated with hepatosplenomegaly (p < 0.0005) even after controlling for area. High plasma levels of sTNFR-I (p < 0.001), sTNFR-II, (p < 0.0001), and sICAM-1 (p < 0.009) were also significantly associated with hepatosplenomegaly, independently of area, in the case of the soluble forms of both TNF receptors. These parameters were negatively related to IL-5. These results suggest that proinflammatory cytokines are involved in the hepatosplenic disease process in infected individuals who have low anti-inflammatory Th2 responses and that sTNFR may be a useful circulating marker for this disease process, perhaps reflecting the level of TNF activity in hepatic tissues.
authors.affiliation: Kenya Medical Research Institute, Division of Vector Borne Diseases, Nairobi.
authors.forename: J K
authors.initials: JK
authors.lastname: Mwatha
authors.forename: G
authors.initials: G
authors.lastname: Kimani
authors.forename: T
authors.initials: T
authors.lastname: Kamau
authors.forename: G G
authors.initials: GG
authors.lastname: Mbugua
authors.forename: J H
authors.initials: JH
authors.lastname: Ouma
authors.forename: J
authors.initials: J
authors.lastname: Mumo
authors.forename: A J
authors.initials: AJ
authors.lastname: Fulford
authors.forename: F M
authors.initials: FM
authors.lastname: Jones
authors.forename: A E
authors.initials: AE
authors.lastname: Butterworth
authors.forename: M B
authors.initials: MB
authors.lastname: Roberts
authors.forename: D W
authors.initials: DW
authors.lastname: Dunne
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D007371:Interferon-gamma / Q000097:blood*; D015848:Interleukin-5 / Q000097:blood*; D008109:Liver Diseases, Parasitic / Q000276:immunology* / Q000473:pathology; D008297:Male; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000473:pathology; D013158:Splenic Diseases / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D015848:Interleukin-5; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma